One of the extraordinary achievements of modern medicine is that physicians can cure 85 percent of children diagnosed with cancer. About 380,000 survivors of childhood and adolescent cancer are living in the U.S, and researchers continue to provide better options in chemotherapy, radiation, and surgical techniques. However, once these therapies end, young cancer survivors’ journeys are far from over.

A research team at The Children’s Hospital of Philadelphia is dedicated to studying the late effects of childhood cancer, which can include secondary cancers, heart disease, infertility, anxiety, depression, and other conditions. They are focused on helping survivors and their families understand what they have been exposed to during treatment, be vigilant about their future risks, and make the transition to an adult care model.

Jill P. Ginsberg, MD, a pediatric oncologist and director of the Cancer Survivorship Program at CHOP, has been fortunate enough to follow some of her patients since they were infants and into their college years, which she described as “really remarkable.” Today, she said, CHOP is at the forefront nationally in terms of cancer survivorship care and late-effects research.

“What sets us apart is that we are truly multidisciplinary,” Dr. Ginsberg said. “Not only does our core team include outstanding nurses, nurse practitioners, and psychologists, but we also have an extended group of subspecialists at CHOP who are keyed into the long-term effects of treatment. Many research initiatives have come out of our group interactions with patients because we collaborate across disciplines.”

For instance, Goli Mostoufi-Moab, MD, MSCE, a dual-certified pediatric oncologist and endocrinologist at CHOP, has taken the lead to study endocrinopathies, which are among the most common late effects of cancer treatment, affecting up to 40 to 60 percent of childhood cancer survivors. Dr. Mostoufi-Moab is especially interested in cancer survivors’ risk for poor bone health due to these numerous endocrine abnormalities, which include abnormal growth, thyroid disorders, and pubertal disorders.

Another research focus is transition readiness of adolescent and young adult survivors of childhood cancer. Wendy Hobbie, RN, MSN, CRNP, FAAN, associate director of the Cancer Survivorship Program, and Lisa Schwartz, PhD, a pediatric psychologist, are finding ways to better facilitate the process so that patients can begin to take control of their own health history and enter the adult health care world better prepared to handle their medical conditions.

“Appropriately, parents are the keepers of their young children’s medical history,” Dr. Ginsberg said. “With guidance from the Cancer Survivorship Program and their parents, survivors in their teen years become empowered to handle their own medical issues, and we help them learn to advocate for themselves.”

The Cancer Survivorship Program’s efforts in fertility preservation are a research priority that has gained national attention. An estimated 35 percent of prepubescent boys are at risk of sterility following cancer treatment, Dr. Ginsberg said. CHOP’s groundbreaking testicular tissue cryopreservation program can offer families hope that their tissue could one day be used to produce viable sperm. Only prepubescent boys at the highest risk for infertility are approached to take part in the program because the procedure remains experimental. All post pubescent boys set to undergo cancer treatment at CHOP, regardless of cancer type, have the opportunity to participate in sperm banking. Moreover, for young female patients at risk for infertility and premature ovarian failure, egg harvesting and ovarian tissue freezing are options available at CHOP.

In addition to these in-house research projects, The Cancer Survivorship Program participates in research on the national level, including studies with the Children’s Oncology Group (COG) chaired by CHOP’s Peter Adamson, MD. The Childhood Cancer Survivor Study (CCSS) involves 34,000 survivors of childhood cancer diagnosed between 1970 and 1999. Many of these study participants are CHOP patients and their families. The study is investigating the long-term effects of cancer and its associated therapies.

“Contributing to these larger studies is important to all of our patients,” Dr. Ginsberg said. “Being a part of a research study is what they’ve grown up doing here at CHOP. It’s a piece of the fabric of these extremely giving patients and their families. They like knowing that they are continuing to be part of the research process to help improve the lives of the next generation of survivors.”

Looking toward the future, Dr. Ginsberg is excited about the possibilities of how the scope of late-effects of cancer will change as new therapies emerge and evolve. Proton therapy, for example, hones in on tumors and spares healthy tissue from radiation exposure. Practical issues that emerge from refined cancer therapy treatments include questions of how will those survivors’ late effects compare with those who received conventional radiation therapy.

“Cancer survivorship and quality of life is an area of intense research,” Dr. Ginsberg said. “As pediatric oncologists, we want to improve the cure rate with less future toxicity, and part of our responsibility is to focus on young patients’ quality of life afterward, as they have long and productive lives to live.”

A study recently published in the Journal of Clinical Endicronology & Metabolism shows a drug approved to treat Crohn’s disease, ulcerative colitis, and related conditions leads to “rapid improvements” in bone density and structure. The study, which was conducted by former and current Children’s Hospital researchers, could offer Crohn’s disease patients a treatment for the growth and bone issues associated with the condition.

A chronic bowel disease, Crohn’s disease (CD) is marked by inflammation of the gastrointestinal tract that can lead to narrowed and blocked intestines and ulcers. Though CD’s cause remains unknown, it may be brought on on by environmental, immunological, and genetic factors. According to the Crohn’s and Colitis Foundation of America, CD affects “as many as 700,000 Americans,” and is seen more often in adolescents aged 15 to 35 years.

In addition to its well-known, abdominal symptoms — such as cramping, diarrhea, and blood in the stool — CD is also associated with an impact on bone health and growth.

To wit, a 2014 review published in the World Journal of Gastroenterology notes “growth failure and impaired nutritional status are seen in [65 to 85 percent] of children and adolescents diagnosed with [Crohn’s disease], and [15 to 40 percent] of these patients continue to suffer from growth deficiency through the course of their disease.”

Examining Infliximab’s Effect on Bone

The current JCEM study investigated the effect the monoclonal antibody infliximab — which is sold under the name Remicade — had on bone density and structure in a cohort of 74 patients aged 5 to 21 years. The researchers evaluated the patients over a 12-month period (at first infusion, 10 weeks, six months, and 12 months), comparing the cohort’s results to data from 650 healthy reference patients who took part in a larger study of bone health.

Infliximab works by blocking tumor necrosis factor alpha (TNF-α), a cell signaling protein that per the JCEM paper, “has direct adverse effects on bone metabolism and plays a pivotal role in CD pathogenesis.”

While previous studies had shown that infliximab treatment had an effect on CD patients’ linear growth, the drug’s “impact on bone modeling has not been established,” the researchers write. They measured changes trabecular bone density and cortical area over the course of the 12-month infliximab treatment, hypothesizing it would improve both measures.

And indeed, Dr. Leonard and colleagues found that the patients’ height, BMI, trabecular bone density, and cortical area all improved, with the data showing “rapid improvements in disease activity.” In addition, the investigators found trabecular bone density improvements were greater in younger patients, which suggests that “childhood provides a window of opportunity for recovery of trabecular and endocortical deficits.”

“We believe this study is important because it is the first to show that blocking this inflammatory cytokine can reverse bone loss,” Dr. Leonard said. “Children can regain bone structure, as well as density.”

Though they caution that their study had limitations and that further research is needed, the researchers note “anti-TNF-α therapy during growth and development is associated with rapid improvements in trabecular [bone density] and cortical structure.”

The most common cause of childhood disability in the world, cerebral palsy affects between 1 and 2 infants per thousand. But despite its prevalence, this neurological condition — which can cause a variety of movement issues and other challenges — tends to be understudied, especially in developing countries.

“For a variety of reasons, children with cerebral palsy tend to have poorer outcomes and a higher prevalence of comorbidities in Botswana compared to those in higher-resource countries,” said study leader David Bearden, MD, a pediatric neurologist at CHOP. “Our research represents a first step toward designing better prevention and treatment of CP in settings such as Botswana.”

Dr. Bearden and his team presented their findings recently at the American Academy of Neurology annual meeting last month in Washington, D.C. The Academy selected one of the investigators’ studies for the “highlights in the field” session.

CP encompasses a variety of motor dysfunctions resulting from brain injury during the fetal period, infancy, or early childhood. Patients with this lifelong condition often have poor muscle control and speech problems.

In their study cohort of 68 children with CP at a referral center in Gaborone, Botswana, Dr. Bearden and colleagues found the most common causes of the condition were prematurity, intrapartum hypoxic events (periods of low oxygen during labor or birth), and infections during infancy. Severe motor impairments were common, with the most severe category occurring in 42 percent of the patients. In the U.S. and European studies, less than 20 percent of children with CP are in the most severe category.

The participants in the study also had high rates of comorbidities, or accompanying conditions. The most predominant was cognitive impairment, found in 83.8 percent of the children, followed by epilepsy (76.5 percent), and visual impairment (45.6 percent). These rates of epilepsy and cognitive impairment were more than double the rates reported in studies of CP in high-resource settings.

When parents and caregivers were interviewed about health beliefs, cultural values, and other barriers to care for children with CP, they expressed major concerns about lack of access to physical therapy, adaptive medical equipment, and good nutrition.

For Dr. Bearden, who has participated in the Botswana/Upenn Partnership since 2007, spending 2 to 3 months there every year, the current studies provide a foundation for further medical work, both in improving health education and devising better public health interventions.

“We need to work closely with doctors in low-resource settings to develop low-cost interventions for children with cerebral palsy,” Dr. Bearden said.

“For example, a community-based rehabilitation approach, teaching parents basic rehabilitation techniques, combined with regular check-ins by a community health worker in the family’s home, is much more likely to succeed that an approach that depends on parents regularly bringing children to the hospital for therapies,” he noted.

Colorectal cancer mainly exists in people older than 50, but it also can occur in young adults who have a genetic condition called familial adenomatous polyposis (FAP). Polyps can begin to form inside the intestinal tract during their teen years. If FAP is not diagnosed and treated, people with FAP have almost a 100 percent chance of developing colorectal cancer.

While FAP is uncommon, understanding its genetic basis could lead researchers at The Children’s Hospital of Philadelphia to better approaches to several kinds of pediatric cancers. In a new study funded by the National Cancer Institute, Andrei Thomas-Tikhonenko, PhD, chief of the Division of Cancer Pathobiology, and colleagues aim to identify subsets of patients who potentially would benefit the most from emerging drugs targeting pathways that are important to colorectal cancer development.

“It’s a study that harnesses the power of cancer genomics and links it to cancer biology and cancer therapeutics,” Dr. Thomas-Tikhonenko said.

Previously, scientists had identified mutations occurring in the APC gene that could lead to FAP and other types of colorectal cancer. An important target of the APC pathway is an oncogene called MYC that as a result becomes hyperactive. Oncogenes play major roles in initiating and maintaining tumor growth. In addition to colorectal cancers, MYC has been implicated in cancers of the cervix, breast, lung, stomach, and pediatric neuroblastoma. MYC has a broad reach, and it is especially good at helping tumors to make blood vessels that are needed for oxygen and energy.

Dr. Thomas-Tikhonenko’s laboratory has dedicated many years of research to studying how MYC works in the context of cancer cell biology and how it interacts with the unique combinations of genetic alterations that appear in colorectal tumors. The Cancer Genome Atlas (TCGA) project, a publicly available catalog of genetic mutations and deletions discovered by scientists worldwide, reported in 2012 that no less than two dozen genes were mutated in a significant number of colorectal cases.

The study team is leveraging data from these cancer genome studies to determine whether or not some of these mutations are redundant, or epistatic. Basically, epistasis is the idea that one gene depends on a second gene because the two genes control a common function. The researchers hypothesize that when a cancer mutation occurs, it picks only one of the genes at work in the same pathway.

Think of epistasis as a series of landmarks along several avenues that all point to the same destination. A roadblock appears at one of the landmarks, diverting traffic. It would be redundant to erect more roadblocks at landmarks further down the same route. Instead, by strategically placing roadblocks on other avenues, the cancer can block normal organ development more efficiently and in doing so direct different aspects of tumor formation and growth.

“What we’re saying is cancer is parsimonious by nature: It doesn’t tolerate redundant mutations; they all happen for a reason,” Dr. Thomas-Tikhonenko explained. “There is stringent selection for useful mutations.”

In the case of a colorectal tumor, the researchers propose that late-stage mutations in the gene called transforming growth factor beta (TGFβ) might be influenced by seemingly unrelated earlier mutations in MYC, typically found in early-stage cancers. They have shown that TGFβ loss helps tumors to build blood vessels, just as MYC hyperactivation does. Since both drive the same tumor trait, could they be epistatic? Indeed, extensive TCGA data mining revealed that MYC and TGFβ mutations almost never occur together.

Conversely, some mutations always seem to co-exist in colorectal tumors, which suggests that the mutations likely act on different, complementary pathways. This analysis was performed in collaboration with Pichai Raman, a bioinformatics scientist from the new Department of Biomedical and Health Informatics at CHOP, and Adam Bass, MD, from the Dana-Farber Cancer Institute in Boston.

Identifying which mutations occur in the same pathway and which occur in parallel is useful because it could help researchers to preselect patients who are likely to respond to certain drug therapeutics. For example, Dr. Thomas-Tikhonenko and his study team will investigate how to maximize impact of drugs within two subtypes of colorectal cancer, called chromosomal instability (CIN) and microsatellite instability (MSI). FAP falls under the CIN class.

Patients with MSI frequently have TGFβ mutations, but they are rare in patients with CIN; MYC mutations generally follow the opposite pattern. Since TGFβ and MYC mutations do not usually appear in the same tumors, the researchers predict that drugs that effectively target MYC could be helpful for FAP but would not have the same impact on patients with MSI.

By the completion of the five-year grant, he expects that scientists will have a new vantage point for colorectal cancer development and treatment. Dr. Thomas-Tikhonenko is looking forward to collaborating on the project with Struan Grant, PhD, a human genetics researcher at CHOP and an associate professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania.

Millions of children will likely experience some kind of unexpected traumatic event, from car crashes to natural disasters to medical emergencies. Many will struggle with psychological challenges during recovery, and parents and physicians may not know how to help them cope emotionally after such frightening episodes.

Researchers at The Children’s Hospital of Philadelphia have developed a web-based intervention called Coping Coach that aims to prevent post-traumatic stress in school-aged children by using game-like activities that they can complete independently or with parent supervision. The study team tested its feasibility in a randomized controlled trial of 72 children ages 8 to 12 who had been admitted to the hospital for an acute medical event. The investigators reported positive results in the Journal of Pediatric Psychology.

“It’s a different way of engaging kids,” said Nancy Kassam-Adams, PhD, a CHOP psychologist and associate director of Behavioral Research at the Center for Injury Research and Prevention (CIRP). “We’ve worked hard to build in items that are useful and therapeutic while keeping it fun. It doesn’t substitute for full-blown mental health treatment. This is for the early days after they’ve been through something difficult, and it teaches kids skills to recover well.”

The online tool starts with a short symptom assessment each time a child logs on. Then the child has the opportunity to interact with different characters, including a misunderstood squirrel named General Malaise. “Mwa-ha-ha-haaaa!” he laughs, and then zaps the town, leaving the townspeople without any feelings. The child must identify different emotions in order to advance to the next module.

The other modules also focus on areas that CIRP researchers and others have shown to be important in intervening early to lower the severity of pediatric post-traumatic stress. These include teaching children to recognize helpful or unhelpful thoughts and behaviors and how not to rely on avoidance as a coping response. An underlying theme that emphasizes the value of social support is embedded throughout the game.

“Each module includes carefully selected intervention targets based in empirical evidence on how post-traumatic stress develops in children,” said Meghan Marsac, PhD, a CHOP psychologist at CIRP, who has co-led the development and evaluation of Coping Coach. “We have applied what we know about the treatment of post-traumatic stress to prevention.”

A group of University of Pennsylvania digital media students created an early version of the game as a summer project five-years-ago and gave it a retro, pixelated vibe. A web design firm in Houston then came on board as collaborators and helped to expand the story and make the tool more robust and interactive. The CHOP Youth Advisory Council shared its feedback at various stages of the game’s development.

The latest version of Coping Coach includes a girl who experiences a scary asthma flare-up, a girl who has been in a car crash, a boy who survived a house fire, and a boy who saw his brother beaten up by other neighborhood kids. The game can be expanded to include other characters to address other sudden, distressing situations.

“Children who use Coping Coach may not see their exact experience, but they get a sense of the range of common traumatic scenarios that kids are exposed to,” Dr. Kassam-Adams said.

For the study, the researchers invited one group of children to log in and play the game within six weeks after being admitted to the hospital. A second group was assigned to a wait list and given the same instructions to complete the online intervention activities following a 12-week research assessment. Both groups completed research assessments over the phone at 6, 12, and 18 weeks so that the researchers could track their symptoms and coping skills over time. They concluded that both groups benefited from Coping Coach participation, which suggests its recommended timing could be flexible.

“Depending on the nature of the event, and the child’s physical/medical condition, some children may not be ready or able to engage in an online intervention immediately post-event,” the authors wrote in their analysis.

The next step is to test Coping Coach in a bigger trial, Dr. Kassam-Adams said. In the meantime, the research team is looking at ways to incorporate new features into the game to encourage children to play it longer and return again and again, perhaps reinforcing the coping strategies. About 60 percent of the children who participated in the study finished the game at least once, and they used it for an average of 52 minutes.

“In our previous evaluation, we have focused on children exposed to unintentional traumatic events,” Dr. Marsac said. “We know that many children also have to deal with trauma resulting from violence, which can bring up unique feelings and challenges. This new research will allow us to examine whether or not the elements of Coping Coach can also be helpful for children experiencing injuries due to violence.”

Once the researchers have enough data to validate Coping Coach’s effectiveness, Dr. Kassam-Adams anticipates that it could be publicly available within the next five years. Since the number of school-aged children who could benefit from a low-cost, web-based post-traumatic stress intervention is enormous, she envisions Coping Coach as a way to fill the gap in resources available to support them during their recovery.

“It could have a huge public health impact on kids exposed to trauma,” Dr. Kassam-Adams said. “They can’t all get in — and not all need to get in — to see a mental health professional. Coping Coach is designed to be preventive. It has the potential to reach so many more kids that even if it helps a little, it will be an important tool.”

With the support of a recent $2.1 million award from the Patient-Centered Outcomes Research Institute (PCORI), The Children’s Hospital of Philadelphia’s James Guevara, MD, MPH, will study the comparative effectiveness of an electronic portal vis-à-vis in-person communication for attention-deficit/hyperactivity disorder (ADHD). Set to be conducted in 15 primary care facilities across Children’s Hospital’s care network, the study will inform ongoing efforts to further involve families’ preferences and goals in ADHD care.

Established by 2010’s Affordable Care Act, PCORI funds comparative effectiveness research, with an eye toward improving “the quality and relevance of evidence available to help patients, caregivers, clinicians, employers, insurers, and policy makers make informed health decisions,” per the PCORI website.

Through September 2014, the Institute has awarded $671 million to support 360 projects in 39 states, according to its 2014 financial report. Dr. Guevara’s award is one of more than 125 — including another to Richard Aplenc, MD, PhD — awarded so far in 2015.

In addition to acting as an attending physician at Children’s Hospital, Dr. Guevara is also an associate professor of Pediatrics and Epidemiology at the University of Pennsylvania’s Perelman School of Medicine, and a founding member of PolicyLab, one of CHOP Research’s Centers of Emphasis. Much of Dr. Guevara’s work has been focused on “improving the delivery of healthcare in primary care settings, reducing health disparities, and translating research findings into practice and policy,” per PolicyLab’s site.

One area of this work has focused on assessing how shared decision-making (SDM) — in which families and clinicians make choices together — can improve outcomes for ADHD patients. A co-investigator on the PCORI project, Alexander G. Fiks, MD, MSCE, has been developing the electronic ADHD portal that will be used to facilitate electronic communication.

As part of this investigation, in 2013 Drs. Guevara, Fiks, and colleagues published a study in Pediatrics that examined parental preferences in ADHD treatment. They found parents’ preferences were associated with treatment initiation. Moreover, the results “suggest that assessing parents’ preferences and goals … is useful for clinicians in understanding which treatment, if any, parents are likely to initiate for their children,” the authors write.

Supported by this new three-year award from PCORI, with his current study Dr. Guevara plans to assess the effectiveness of the ADHD portal versus the ADHD portal in combination with a care manager in communicating patients’ and families’ treatment goals. The researchers hope to enroll roughly 300 children between the ages of 5 to 12 years, who will be randomized to one of the two groups. Parents will complete ADHD outcome measures at 0, 3, 6, and 9 months.

Dr. Guevara and colleagues also plan on using feedback to improve the study. The will ask various stakeholders — including clinicians, as well as parents and teachers of children with ADHD — to advise the research team on study questions, the investigation’s design, and how the results are disseminated.

“Findings from this study,” Dr. Guevara notes, “will inform the use of communication strategies to share family preferences and goals among parents, teachers, and clinicians of children with ADHD.”

To read more about PolicyLab’s work on communications strategies and provider-patient relationships, see the Center’s website.

At this point, about 2.1 million adolescents worldwide are living with HIV. While recent data has shown that AIDS-related mortality declined from 2005 to 2012 for adults and children, adolescent mortality has increased by 50 percent. What is creating such a huge equity gap in treatment for adolescents?

In an editorial published in JAMA Pediatrics, Dr. Wood and colleagues suggest that adolescents living with HIV are a “generation at stake.” A significant barrier to achieving their optimal care is that youth with HIV who are older than 13 often are treated as adults, which fails to recognize that adolescence is a unique and distinct transition of physical, psychosocial, and neurocognitive development. These years also are a crucial time for youth who are not yet HIV positive but are at high risk for infection.

“They are still developing their brains, and they are subject to intense social pressures,” Dr. Wood said. “Those things can work together for youth who are not yet infected with HIV to increase their risk of becoming HIV positive through risk-taking behaviors. Or, for youth who have been born with HIV, their adherence to antiretroviral therapy is going to face significant challenges during this adolescent period.”

As an adolescent medicine expert, Dr. Wood recognizes that the concept of future orientation — teens’ ability to think about how poor adherence when they are feeling well will eventually impact their future health — is a difficult concept for most teens with chronic conditions to grasp. But that should not relegate the teen years as a tumultuous time of bad choices. Instead, she said, we must begin to prioritize adolescent HIV care as a “dynamic process of overlapping stages” and develop systems tailored to help youth navigate this continuum.

Then researchers can begin to pinpoint and pilot test interventions targeted at different levels of that cascade:

finding youth who are HIV positive

increasing uptake of testing

facilitating linkage to care interventions

looking at the barriers to prescribing antiretroviral therapy

identifying the challenges and facilitators for adolescents to stay in care and adhere to antiretroviral therapy throughout their life cycle.

Dr. Wood especially is interested in exploring how to use and strengthen adolescents’ social support, which includes family, partners, and other people in their social network, to make improvements in these areas. Part of a program at CHOP called the Adolescent Initiative uses an integrated, medical case management model that emphasizes social support when helping youth to become more knowledgeable and competent in managing their HIV. Oftentimes, this means working with youth who have been left homeless due to stigma and discrimination related to their sexual orientation or gender identity.

“We’re doing work to optimize the social support that adolescents have because we can care for them while they’re in the clinic, but in the month or months in between when we see them, they must rely on the support that they have in their lives to be able to sustain treatment,” Dr. Wood said. “Many of our youth are thinking about where are they going to sleep that night and how are they going to eat. The stress of survival may outweigh their ability to think about taking a medication.”

Hearing firsthand from youth living with HIV about their daily difficulties has prompted Dr. Wood to pursue some important research questions: What factors in adolescents’ lives may challenge their ability to stay adherent to their therapy and stay suppressed from a viral load standpoint? And over time, how does housing, social support, substance abuse, and mental illness play into our ability to provide optimal care for youth living with HIV? Another one of her research priorities is looking at ways to increase uptake of HIV pre-exposure prophylaxis.

“We live in an amazing time,” said Dr. Wood, who has 17 years of experience in the area of HIV and sexual health preventative care. “Keeping people adherent with their antiretroviral therapy can reduce their risk of transmitting to their partners. But we also now know that we can give antiretroviral medicine to our negative youth and keep them from becoming HIV positive.”

Prior to starting her Adolescent Medicine fellowship, Dr. Wood was a site investigator at CHOP for Project PrEPare, which aims to examine the acceptability and feasibility of daily medication to prevent HIV for young men who have sex with men. The study began in 2012 and included approximately 100 participants between the ages of 15 and 17 from 12 cities across the U.S. Now in its final stages, the project is a prime example of adolescent-specific research that will be essential to advancing HIV care and prevention for youth in years to come.

“We need to begin to build an adolescent care competent world in HIV,” Dr. Wood said.

Seen most often in preterm infants weighing 1250 grams or less, retinopathy of prematurity (ROP) is a condition in which growth of abnormal blood vessels in the eye can damage or even detach the retina, leading to severe vision loss and in some cases blindness. While most cases of ROP do not require treatment, roughly 10 percent do. Early detection is key in infants with severe ROP. The American Academy of Ophthalmology recommends screening by an experienced ophthalmologist for all infants who weight less than 3.3 pounds at birth or are born at or before 30 weeks.

Unfortunately, ophthalmologists experienced in detecting ROP are not always on hand when a preterm baby is born. The U.S. has seen a decline in ophthalmologists in recent years, with rural areas being most severely affected. In addition, some areas of the world where more preterm infants are surviving than ever before — such as Latin America and Eastern Europe, which also have a dearth of ophthalmologists — have higher rates of ROP-related blindness than the U.S.

Dr. Quinn’s project, however, offers a potential solution to this problem. He has been leading a collaboration among 13 North American clinical centers with neonatal intensive care. The e-ROP Cooperative Group has been investigating the feasibility of a remote telemedicine system to detect ROP in newborns.

Last year, Dr. Quinn and his team published the study results in JAMA Ophthalmology. They showed that trained non-physician evaluators who studied retinal images transmitted to computer screens at a remote reading center were able to identify infants who required specialized evaluation for ROP by an ophthalmologist.

“This study provides validation for a telemedicine approach to ROP screening and could help prevent thousands of premature babies from going blind,” said Dr. Quinn when the study was published. “Telemedicine potentially gives every hospital access to excellent ROP screening.”

While many of NIH’s institutes are working on telemedicine projects, a more recent, “very promising” area of research is mHealth, which takes advantage of mobile technologies, Dr. Collins noted. mHealth makes health “transportable, where people are walking around with their own potential telehealth gadgets in their pockets,” he said.

He then went on to briefly describe the e-ROP project, which he said uses technology in intensive care units to assess whether newborns have ROP, “by basically taking photographs, and then sending them to an expert across the country, to say this baby needs treatment, that one doesn’t.”

“Our NIH portfolio has shifted dramatically in the direction of mHealth, mobile health, using cellphone technology,” continued Dr. Collins, who added that mHealth “is bursting with potential for … maintaining health or for perhaps using this to monitor chronic illness … that’s such a great opportunity for medicine.”

Since the publication of the e-ROP study in JAMA Ophthalmology last year, Dr. Quinn has hardly rested on his laurels. In addition to his work as an attending surgeon in the Division of Ophthalmology, Dr. Quinn and his team have published a series of ROP-related papers, including two more in JAMA Ophthalmology. In March he co-authored a study on the development of a prediction model of ROP, and in June contributed to another on a centralized system for grading digital images of ROP.

Researchers from The Children’s Hospital of Philadelphia have found a clear-cut and persistent gender bias in the provision of treatment for idiopathic short stature (ISS) with recombinant human growth hormone treatment. The work, which was published recently in Scientific Reports, shows short boys are three times more likely than short girls to receive recombinant human growth hormone treatment for ISS.

The statistical definition for ISS (short stature from an unknown cause) height corresponds to the shortest 1.2 percent of the U.S. population. The study aims at understanding the origins of the disparities in the management of short stature.

“Social pressures regarding height seem to affect males more than females, at least in the U.S.,” said the study’s leader Adda Grimberg, MD, a pediatric endocrinologist at Children’s Hospital and a senior fellow of the Leonard Davis Institute of Health Economics at the University of Pennsylvania. “In the absence of an underlying condition, treating short children with recombinant human growth hormone represents medicalization of a physical trait.”

The research team looked at the health records from 28 primary care practices in the CHOP pediatric network, comprising 189,280 patients, and compared them to 93,736 patients from the four U.S. pediatric growth hormone registries. All the subjects were children and adolescents (up to age 20).

In the primary care population, 2,073 subjects (1.1 percent of the total) had heights below the threshold for idiopathic short stature. There were no gender differences in the prevalence of height below this threshold, or in the distributions of height in the entire primary care population. In contrast, among patients receiving recombinant human growth hormone for ISS, 74 percent were male. Among patients who received the hormone for all diagnoses, 66 percent were male. At the time of initiating growth hormone for idiopathic short stature, treated boys outnumbered girls for every year of age starting at age one, but the biggest differences occurred around puberty, when late bloomers and limited remaining time for potential medical intervention raise concern.

“Growth is an important sign of child health, so growth failure merits equal consideration for both boys and girls,” Dr. Grimberg said. “Gender bias in treatment may have doubly undesirable effects — short girls who have an underlying disease may be overlooked, while short healthy boys may receive overzealous, unnecessary treatment with an expensive drug that requires years of nightly injections and has potential side effects.”

In previous research, Dr. Grimberg found that proportionally more girls who were referred for evaluation of short stature were much more likely to have an underlying disease than boys who were referred. “The gender bias in referral and treatment suggests that diagnoses of underlying diseases are more likely to be delayed or missed altogether in short girls, and this suggests missed opportunities to address those conditions, not all of which require growth hormone treatment,” she said.

For more information, and for a link to the study in Scientific Reports, published online June 9, 2015, click here.

Noting “vaccine-preventable diseases remain a significant threat to children’s health,” in a recent editorial The Children’s Hospital of Philadelphia’s Kristen A. Feemster, MD, MPH, MSHP, calls for “ongoing vigilance.” Dr. Feemster’s editorial, which was published recently in JAMA Pediatrics, reviews vaccines’ successes while also pointing out that exemption laws and increasing vaccine hesitancy mean “the success of vaccines can be fragile.”

Dr. Feemster’s article follows the publication of a study — also in JAMA Pediatrics — showing the effect the introduction of a new vaccine had on invasive pneumococcal disease (IPD). A team of researchers led by the New York City Department of Health’s Andrea C. Farnham, MPH, evaluated the effect the 13-valent pneumococcal conjugate vaccine (PCV13) — which was introduced in 2010 and contains 6 more serotypes than the previous pneumococcal vaccine (PCV7) — had on IPD rates in a population of children younger than five years of age.

The researchers showed the vaccine decreased IPD incidence by 69.6 percent, from 21 cases per 100,000 to 6.4 cases per 100,000. Pneumococcal infection can cause a variety of conditions, from the routine (as in ear infections) to serious conditions like meningitis.

Dr. Feemster’s JAMA Pediatrics article comes on the heels of a measles resurgence, with 169 people across the country reported to have the disease between January 1 and May 1, 2015, according to the CDC. In a press briefing about the measles outbreaks, the CDC’s Anne Schuchat, MD, noted most of the people who have been reported to have measles had not been vaccinated. “This is not a problem with the measles vaccine not working,” Dr. Schuchat said. “This is a problem of the measles vaccine not being used.”

Dr. Feemster’s editorial echoes this, as she notes “events show us that the success of vaccines can be fragile; the measles cases associated with Disneyland were preceded by 644 cases in 2014. In 2012, there were more than 40,000 cases of pertussis, the largest number since 1960. These events have garnered media attention and provide a dramatic reminder that vaccines remain an important and necessary health tool.”

“Fear has led to hesitancy and is now influencing the push to make it more difficult to refuse vaccination. Fear should not be driving policy,” Dr. Feemster notes in her JAMA Pediatrics editorial. “Instead, a real-time example of the effect of a successful immunization program should move us to continue to advocate for strong vaccine policies that support uptake of all routinely recommended vaccines.”

Many families of premature infants quickly become familiar with a powerful research tool called a randomized clinical trial (RCT). Neonatologists may invite them to participate in RCTs, as they investigate ways to help prevent, treat, and manage the myriad complications that can occur when these babies’ organs are not ready for life outside their mothers’ wombs.

In a RCT, study participants are randomly assigned to two or more groups, which helps to reduce any potential bias and compare research results. For example, one group receives a new drug being tested, and one group receives a placebo, no treatment, or a different drug. Parents, however, may wonder if the decision to include their newborns in a RCT could be associated with any detrimental differences in their outcomes.

A research letter published in JAMA by several neonatologists from The Children’s Hospital of Philadelphia and the University of Pennsylvania may help to alleviate these concerns. They reported results from a study of 5,000 extremely preterm infants and determined that important in-hospital outcomes, such as severe brain injury and a chronic lung disorder called bronchopulmonary dysplasia, were neither better nor worse in infants enrolled in RCTs compared with infants who were eligible but not enrolled in RCTs.

“These results are important, as they provide reassurance that participating in randomized trials is not detrimental to preterm infants,” said Elizabeth E. Foglia, MD, an attending neonatologist with the Division of Neonatology at CHOP, who co-authored the letter.

The new findings are in line with previous research of adults and older children that demonstrated no significant differences in outcomes between trial participants and nonparticipants who were treated similarly outside trials, the authors pointed out.

“Many therapies that are commonly used in preterm and sick infants have never been rigorously tested, and novel interventions are being developed all the time,” said Dr. Foglia, who also is an instructor in Pediatrics at the Perelman School of Medicine, University of Pennsylvania. “The only way we can know with confidence that a given therapy is safe and effective in our patients is by performing well-designed and appropriately regulated randomized trials.”

Several RCTs involving premature infants are underway at The Children’s Hospital of Philadelphia, such as the Sustained Aeration of Infant Lungs Trial (SAIL) trial, which is looking at the standard of care for resuscitation of these babies at delivery. Another RCT is comparing two oral feeding schedules for premature infants, and researchers are collecting data on milk transfer, sucking strength, growth, and medical complications.

As a curious 12-year-old on a long cross-country trip, Carole Marcus found a slim book in her family car’s backseat written by William C. Dement, MD, PhD, a pioneering sleep researcher. Little did she know as she began flicking through its intriguing pages that one day she would receive a prestigious sleep medicine career award named in his honor.

On June 8, Carole Marcus, MBBCh, received the 2015 William C. Dement Academic Achievement Award at the Annual Meeting of the Associated Professional Sleep Societies held at the Washington State Convention Center. The award recognizes members of the sleep field who have displayed exceptional initiative and progress in the areas of academic research.

“I am extremely honored,” said Dr. Marcus, who has directed the Sleep Center at The Children’s Hospital of Philadelphia since 2003. “Dr. Dement is the father of sleep medicine and someone I really admire. He has taught me to be open to new ideas. A lot of research is not believing what you see and following the path that your research takes, even if it’s an unexpected turn.”

Dr. Marcus has spent most of her career studying the physiology of pediatric obstructive sleep apnea (OSA) and trying to understand the factors leading to airway collapse in sleep. During OSA, a child stops breathing usually because there is a blockage from enlarged tonsils or adenoids, causing a brief arousal that increases muscle tone, opens the airway, and allows the child to resume breathing.

Through her research, Dr. Marcus has identified that most children have very active upper airway neuromotor reflexes that allow them to compensate when their airways become narrowed during sleep. Children who experience OSA, however, do not appear to have these reflexes. It remains unclear whether they lost them or never developed them.

Recurrent nightly episodes of sleep disruptions caused by OSA have been associated with adverse behavioral, cognitive, quality of life, and health outcomes in children. Dr. Marcus was the first author of a large, multicenter study published in the New England Journal of Medicine in 2013 called the Childhood Adenotonsillectomy Study for Children With OSAS (CHAT).

Results of the study showed that study participants who underwent surgery to remove their adenoids and tonsils had notable improvements in behavior, quality of life, and other symptoms compared to those treated with “watchful waiting” and supportive care, but the researchers did not find any improvements in cognition.

When Dr. Marcus was in medical school in South Africa during the early 1980s, not much was known about OSA and especially about how it affected children. She remembers medical students receiving only one lecture on sleep. Fortunately, during her residency in pediatrics at the State University of New York, one of the senior doctors had just written one of the earliest case reports on pediatric OSA. During rounds, he would point out patients, many with Down syndrome, who had periods of airway obstruction during sleep.

Dr. Marcus recalls one case in particular. She was called to the emergency room to perform her first intubation, which involves the placement of a flexible tube into the windpipe to maintain an open airway. The child had cerebral palsy and could not breathe after receiving sedation. But just as Dr. Marcus was about to begin the procedure, an attending physician asked her to wait a moment.

“He repositioned the child’s jaw and showed that the child had obstructive sleep apnea,” Dr. Marcus said. “And so I didn’t get to do my intubation. But, in fact, once we treated the obstructive sleep apnea, the child changed dramatically. He went from being severely impaired to a happy, smiley, playful child who had moderate function. That really caught my attention.”

Dr. Marcus continues to find practicing sleep medicine extremely gratifying because she often sees how diagnosing sleep problems and then recommending appropriate therapies can make a huge difference in patients’ and families’ lives. She directs a sleep laboratory at The Children’s Hospital of Philadelphia’s main campus and two satellite sites in suburban Philadelphia and New Jersey, with a total of 14 beds. Dr. Marcus and a team of sleep specialists and technologists perform sophisticated sleep studies to help children of all ages — from premature infants to teens — who have a wide range of sleep conditions, including narcolepsy and suspected seizures during sleep.

The sleep field has come a long way since the childhood road trip when she read about Dr. Dement’s homemade sleep lab in his basement, and many of those advancements are due to Dr. Marcus’ enduring pursuit of knowledge in sleep medicine. Dr. Marcus currently is excited about a new study, called Steroids for Pediatric Research in Kids (SPARK), that she is leading at CHOP to look at the effects of nasal steroids on treating OSA as an alternative to surgery.

“Sleep is just so fascinating,” Dr. Marcus said. “We’re in an era where we have the gene for so many diseases, and yet we don’t fully understand why people sleep. Sleep remains one of the big enigmas in medicine. So little research has been done in pediatric sleep, and there is so much to find out.”